近日，法国索邦大学的Pascal Silberzan及其研究团队取得一项新进展。经过不懈努力，他们证实了集体接触导引下双向细胞收缩的出现。相关研究成果已于2024年5月27日在国际知名学术期刊《自然—物理学》上发表。

据悉，定向的集体细胞迁移对形态发生、伤口愈合和癌症进展至关重要。尽管微环境的分子各向异性引导了这种迁移，但其对细胞流动模式的影响仍未被探索。

该研究团队展示了在双向通道中，亚细胞微沟槽如何引发集体迁移的极性模式，其宽度可达数百微米。这种定向的聚落形态是在体外对人类支气管上皮细胞融合单层进行观察时发现的，而在无特征基底上，其动力学表现是混沌的。

活性极性流体的流体动力学理论及其对应的数值模拟，解释了这种从无序到有序划分的转变，并进一步预测了与沟槽相关的各向异性摩擦降低了转变阈值，这一点已通过实验得到了研究人员的证实。因此，环境的微观各向异性不仅指导集体细胞沿着基质易轴运动，还塑造了细胞迁移的模式。

这种由集体接触引导诱导的流动模式与由超细胞约束导致的流动模式不同，显示出集体迁移受到微环境不同长度尺度的影响。这一发现为组织工程应用提供了一种，指引细胞向特定几何形状和功能迁移的策略，如类器官形态发生。

附：英文原文

Title: Emergence of bidirectional cell laning from collective contact guidance

Author: Lacroix, Mathilde, Smeets, Bart, Blanch-Mercader, Carles, Bell, Samuel, Giuglaris, Caroline, Chen, Hsiang-Ying, Prost, Jacques, Silberzan, Pascal

Issue&Volume: 2024-05-27

Abstract: Directed collective cell migration is central to morphogenesis, wound healing and cancer progression. Although the molecular anisotropy of the microenvironment guides this migration, its impact on cell flow patterns remains unexplored. Here we show that subcellular microgrooves elicit a polar mode of collective migration in bidirectional lanes, whose widths reach hundreds of micrometres. This directed form of flocking is observed in vitro with a confluent monolayer of human bronchial epithelial cells whose dynamics is chaotic on featureless substrates. A hydrodynamic theory of active polar fluids and corresponding numerical simulations account for this disorder-to-laning transition and further predict that anisotropic friction associated with the grooves lowers the transition threshold, which we confirm experimentally. Therefore, the microscopic anisotropy of the environment both directs collective cell motion along the substrate easy axis and shapes cell migration patterns. The flow patterns induced by this collective contact guidance are different from those resulting from supracellular confinement, demonstrating that collective migration is impacted by the different length scales of the microenvironment. Our findings offer a strategy for directing cells to specific geometries and functions in tissue engineering applications such as organoid morphogenesis.

DOI: 10.1038/s41567-024-02510-3

Source: https://www.nature.com/articles/s41567-024-02510-3